Our goal is to understand the underlying mechanisms involved in regulating lineage specification of hematopoietic stem cells (HSC) and vascular angioblast cells from mesoderm during embryogenesis. Towards this goal we have chosen etsrp, one of the earliest lineage specific genes involved in hematopoietic and vascular development, as an entry point to dissect this process in zebrafish. Specifically, we will analyze functions of etsrp in definitive hematopoiesis, elucidate mechanisms regulating its specific expression, identify and characterize its biological targets. Since genes we propose to study are highly conserved between fish and mammals information obtained from zebrafish should be useful for understanding human pathogenesis and designing better therapeutics for hematological and vascular diseases. PUBLIC HEALTH RELEVANCE: Zebrafish is a popular model organism for studying development, physiology and human diseases. We use state of the art technologies to identify and characterize essential new genes required for the formation of blood stem cells and vascular progenitors in zebrafish. Since these genes are highly conserved between fish and human our studies will provide valuable information for understanding human hematopoietic and vascular diseases and assisting design of novel therapeutic approaches.